The HIV-protease enzyme is absolutely essential for the replication and dissemination of HIV throughout the body (Navia M. A. and McKeever B. M., Ann. New York Acad. Sci., 1990; 616:73-85) and has become an extremely important target for the design and development of anti-HIV therapeutic agents (von der Helm K., Biol. Chem. 1996; 377:756-774). Several peptidomimetic HIV protease inhibitors have been successfully developed (such as indinavir, saquinavir, ritonavir, and nelfinavir), which demonstrate significant clinical success in lowering plasma viral load, reducing the onset to AIDS, and decreasing the frequency of opportunistic infections (Deeks S. G., Smith M., Holodniy M., and Kahn J. O., JAMA. 1997; 277:145-153).
Yet the current HIV protease inhibitors by their peptidomimetic nature have relatively poor solubility, high biliary excretion, limited bioavailabilities and significant liver metabolism. These drawbacks in turn increase the need for high doses of a drug, which increases the frequency of various side effects and multiple drug interactions (Barry M., Gibbons S., Back D., and Mulcahy F., Clin. Pharmacokinet., 1997;32: 194-209). More importantly, resistance to the current HIV protease inhibitors has emerged (Shock H. B., Garsky V. M., and Kuo L., J. Biol. Chem., 1996;271:31957-31963) resulting in treatment failures (Fatkenheuer G., Theisen A., Rockstroh J., Grabow T., et al., AIDS, 1997;11:F113-F116). From this discussion, it is apparent that while HIV protease is an excellent antiviral target for the treatment of HIV infection and AIDS, there is a need to identify non-peptide inhibitors with improved pharmacological properties and which are not cross resistant with the current drugs (Wallace R. W., DDT, 1997;2:83-84).
U.S. Pat. No. 5,789,440 recites non-peptidic HIV protease inhibitors of formula A 
The patent is hereby incorporated by reference. Excellent HIV protease inhibition was achieved, but the antiviral activity at the cellular level was in some cases less than desired for an ideal therapeutic agent due to poor overall pharmacological properties (Tummino P. J., Vara Prasad J. V. N., Ferguson D., Nauhan C., et al., BioOrganic and Med Chem., 1996;4:1401-1410). These efforts however led to a core structure B where R1 and R2 were alkyl groups filling the 
S1xe2x80x2 and S2xe2x80x2 pockets, respectively, and the phenyl of the phenethyl group at C6 filled the S2 pocket very efficiently. This core structure was recognized as a valuable platform for additional study (Tait B. D., Hagen S., Domagala J. M., Ellsworth E. L., et al., J. Med. Chem., 1997;40:3781-3792).
Additional dihydropyrones C were reported when it was unexpectedly discovered that certain groups which reduced lipophilicity judiciously placed at R1-R5 led to greatly 
improved antiviral cellular activity. See U.S. Pat. No. 5,834,506. The patent is hereby incorporated by reference. Among the preferred compounds were those where R1 and R5 were OH, NH2, or CH2OH. In such cases, the preferred R4 included a small alkyl chain or ring and R6 was methyl. In addition to improved cellular antiviral activity, the compounds also showed good pharmacokinetics in animals relative to the less-polar substituted compounds. These compounds were also not cross resistant with current HIV Protease inhibitors (Hagen S. E., Vara Prasad J. V. N., Boyer F. E., Domagala J. M ., et al., J. Med., 1997;40:3707-3711; Vander Roest S., Wold S., and Saunders J., 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Sep. 28-Oct. 1, 1997, Toronto, Canada. Abstract I-84; Domagala J. M., Boyer F., Ellsworth E., Gajda C., et al., 5th Conference on Retroviruses and Opportunistic Infections, Feb. 1-5, 1998, Chicago, Ill. Abstract 638).
While the compounds C were notable for their improved pharmacological properties relative to the non-polar substituted core molecules B, these highly favorable properties were conferred directly by the use of OH, NH2 and NR2 groups placed on the lipophilic rings. The rings themselves were important for binding to the enzyme xe2x80x9cpocketsxe2x80x9d and for holding the t-butyl group and the groups R1-R3 and R5 in their proper places within the enzyme""s active site.
This hereby incorporates by reference 5888L1-01-TMC filed on even date herewith entitled xe2x80x9cA Method of Making Dihydropyrone HIV Protease Inhibitorsxe2x80x9d by Victor Fedij et al.
The present invention relates to compounds or pharmaceutically acceptable salts thereof of formula I, shown below: 
wherein:
R1 is H, a straight or branched alkyl of 1-6 carbons or a carbocycle of 3-6 carbons,
R2 is H, a straight or branched alkyl of 1-5 carbons or a carbocycle of 3-6 carbons;
R3 is H [C(R9)2]nOR, [C(R9)2]nN(R)2, [C(R9)2]nN(R9)COR, [C(R9)2]nCO2R, [C(R9)2]n(O)COR, [C(R9)2]nCON(R)2, [C(R9)2]nOC(O)N(R)2, [C(R9)2R], [C(R9)2]nN(R9)CON(R)2, [C(R9)2]nN(R9)CO2R, [C(R9)2]nOSO2N(R)2, [C(R9)2]nN(R9)SO2OR, [C(R9)2]nN(R9)SO2N(R)2, [C(R9)2]nOSO2R, [C(R9)2]nN (R9)SO2R, [C(R9)2]nSOpR, [C(R9)2]nN(R9)CSN(R)2, [C(R9)2]nN(R9)C(xe2x95x90NR9)N(R)2, [C(R9)2]nSO2N(R)2, [C(R9)2]nC(NR9)N(R)2, [C(R9)2]nCOR, O[C(R9)2]mOR, N(R)[C(R9)2]mOR, F, Cl, Br, CF3, CN, or xe2x95x90O when Ar is Het;
R4, R5, and R6 are independently H, a straight or branched alkyl of 1-6 carbons, a cycloalkyl of 3-6 carbons, [C(R9)2]nOR, [C(R9)2]nN(R)2, F, Cl, Br, CN, CF3, xe2x95x90O when Ar is Het; [C(R9)2]nN(R9)COR, [C(R9)2]nSOpR, [C(R9)2]nR, [C(R9)2]n(O)COR, O[C(R9)2]mOR, N(R)[C(R9)2]mOR, [C(R9)2]nN(R9)CON(R)2, [C(R9)2]n(O)CON(R)2, [C(R9)2]nNR9CO2R, [C(R9)2]nCOR, [C(R9)2]nCO2R, [C(R9)2]nCON(R)2, [C(R9)2]nN(R9)SO2R, [C(R9)2]nSO2N(R)2, [C(R9)2]nN(R9)SO2OR, [C(R9)2]nOSO2N(R)2, [C(R9)2]nN(R9)SO2N(R)2, [C(R9)2]nC(xe2x95x90NR9)N(R)2, [C(R9)2]nN(R9)C(xe2x95x90NR9)N(R)2, [C(R9)2]nHet;
any two of R1-R3 or R4-R6 may together form a ring of 5-6 total atoms which may contain 0-3 heteroatoms;
X is NH, NR8;
f is an integer of from 0 to 3;
n is an integer of from 0 to 3;
m is an integer of from 2 to 4;
p is an integer from 1 to 2;
R7 is a straight or branched alkyl of 1-6 carbons or a carbocycle of 3-6 carbons;
R8 is a straight or branched alkyl of 1-6 carbons, a carbocycle of 3-6 carbons, (CH2)nPh, or a (CH2)nheterocycle of 5-6 atoms containing 1-4 heteroatoms and wherein the (R)2 in N(R)2 optionally forms a heterocycle containing the nitrogen, all optionally substituted by F, Ci, Br, OR9, CN, CO2R9, N(R9)2, NR9COR9, CF3, or xe2x95x90O; or an alkyl group bearing polar functionalities, optionally including OH, NH2, CN;
R1 and R8 may together form a ring of 5-6 atoms;
R is independently H, a straight or branched alkyl of 1-6 carbons, (CH2)nPh, or a (CH2)nheterocycle of 5-6 atoms containing 1-4 heteroatoms and wherein the (R)2 in N(R)2 optionally forms a heterocycle containing the nitrogen, all optionally substituted by F, Cl, Br, OR9, CN, CO2R9, N(R9)2, NR9COR9, CF3, or xe2x95x90O;
R9 is independently H, a straight or branched alkyl of 1-4 carbons, or phenyl;
R10 is independently H, a straight or branched alkyl of 1-4 carbons, F, Cl, Br, OR9 or N(R9)2;
R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 may be alkene or alkyne of from 2 to 6 carbon atoms;
Ar1 and Ar2 are independently phenyl or Het;
Het is a heterocycle of from 5-6 atoms having from 1-4 heteroatoms or a fused heterocycle of from 9-10 atoms having 1-3 heteroatoms
wherein the heteroatoms are independently N, O or S,
A compound, which upon administering to mammals such as a human being converts into a compound according to Formula, I is within the scope of this invention.